DPP-4 Inhibitors

Impact on glycemic control and cardiovascular risk factors

  1. Dror Dicker, MD
  1. Internal Medicine D and Obesity Clinic, Hasharon Hospital, Rabin Medical Center, Tel Aviv University, Tel Aviv, Israel
  1. Corresponding author: Dror Dicker, daniel3{at}013.net.

The first dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin was approved in 2006 as treatment for diabetes concurrently with lifestyle changes. A combined product of sitagliptin and glucophage was approved by the U.S. Food and Drug Administration in 2007. The second DPP-4 inhibitor, saxagliptin, was approved in the U.S. It was approved both as monotherapy as well as in combination with metformin, sulfonylurea, or thiazolidinedione. The use of a DPP-4 inhibitor called vildagliptin was approved in Europe and Latin America also as a combination with metformin, sulfonylurea, or thiazolidinedione. Two other DPP-4 inhibitors are also available (linagliptin and alogliptin). In this review, we will elaborate only on the first three drugs (sitagliptin, saxagliptin, and vildagliptin).

The different DPP-4 inhibitors are distinctive in their metabolism (saxagliptin and vildagliptin are metabolized in the liver and sitagliptin is not), their excretion, their recommended dosage, and the daily dosage that is required for effective treatment. They are similar, however, when comparing their efficacy regarding lowering HbA1c levels, safety profile, and patient tolerance.


The influence of DPP-4 inhibitors on the blood levels of HbA1c as monotherapy or in combination with other oral antidiabetes drugs was tested in multiple trials lasting 12–52 weeks. The results of these important trials were reviewed by Davidson (1) and will be summarized here briefly. Treatment with sitagliptin showed an average decrease in HbA1c levels of 0.65% after 12 weeks of treatment, 0.84% after 18 weeks of treatment, 0.85% after 24 weeks of treatment, 1.0% after 30 weeks of treatment, and 0.67% after 52 weeks of treatment. Treatment with saxagliptin showed an average decrease in HbA1c levels of 0.43–1.17%. Treatment with vildagliptin showed an average decrease in HbA1c levels of 1.4% after 24 weeks as monotherapy in a subgroup of patients with no prior oral treatment and …

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